The major objective will be to correlate the immunologic reactivity of human histocompatibility antigens with their chemical and molecular structure. Thus, efforts will be continued to ascertain whether protease derived fragments derived from HLA antigens will still form a molecular complex with beta2-microglobulin. Efforts will also be made to assess the extent of any hypervariable amino acid sequence region(s) on HLA antigens and possibly on DR beta-chains. Attempts will be made to assess the immunogenicity of protease-derived antigen fragments which specifically bind to insolubilized xenoantisera by injecting such complexes into animals and determine whether they elicit the production of specific xenoantisera directed to histocompatibility antigens. Additional efforts are directed at determining the role of carbohydrates in expressing allotypic determinants of human histocompatibility antigens. To this end, RNA isolated from cultured B-lymphoid cells will be used to initiate antigen synthesis in a cell-free system lacking any glycosylation. Well characterized HLA and DR xenoantisera will be used to determine whether they can specifically react with nonglycosylated antigenic products and then to assess whether such antigens can evoke production of specific antibodies to histocompatibility antigens by injecting the complexes into animals.